1-Hydroxybenzotriazole → 5-(2-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)ethylcarbamoyl)pyrazine-2-carboxylic acid
Reaction equation
[N:1]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]=[CH:3][C:2]=1[C:10]([OH:12])=[O:11].C1C=CC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CCN(C(C)C)C(C)C.[NH2:44][CH2:45][CH2:46][N:47]1[CH:51]=[CH:50][C:49]([C:52]2[CH:59]=[CH:58][C:55]([C:56]#[N:57])=[C:54]([Cl:60])[CH:53]=2)=[N:48]1>C(Cl)Cl.O>[Cl:60][C:54]1[CH:53]=[C:52]([C:49]2[CH:50]=[CH:51][N:47]([CH2:46][CH2:45][NH:44][C:7]([C:5]3[N:4]=[CH:3][C:2]([C:10]([OH:12])=[O:11])=[N:1][CH:6]=3)=[O:9])[N:48]=2)[CH:59]=[CH:58][C:55]=1[C:56]#[N:57]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 2
Procedure
Pyrazine-2,5-dicarboxylic acid (0.53 g; 3.18 mmol), anhydrous HOBt (0.43 g; 3.18 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.61 g; 3.18 mmol) and DIPEA (0.55 ml; 3.18 mmol) were dissolved in 5 ml of dry DCM. 4-(1-(2-Aminoethyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (0.6 g; 2.12 mmol) and DIPEA (0.55 ml; 3.18 mmol) were dissolved in 5 ml of dry DCM and added dropwise to the previous mixture. The reaction mixture was stirred overnight after which pyrazine-2,5-dicarboxylic acid (0.27 g; 1.59 mmol), anhydrous HOBt (0.52 g; 3.81 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.41 g: 2.12 mmol) and DIPEA (0.37 ml; 2.12 mmol) were added to drive the reaction to completion. After 2.5 h the mixture was diluted with 20 ml of DCM. After addition of 10 ml of water, the product precipitated and was filtered yielding 0.42 g of crude product which was used without further purification.
Workup
- additionadded dropwise to the previous mixture
- additionwere added
- customthe reaction to completion
- customthe product precipitated
- filtrationwas filtered
Sources & evidence
- ORD record
- ord-b7d685bd70b7453380c670688764bbc2
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08975254B2
Reaction notes
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